CAR-T Therapy for Non-Hodgkin's Lymphoma

Recruiting at 34 trial locations

Overseen By Study Contact, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Janssen Research & Development, LLC

Must be taking: Anti-CD20 antibody

Disqualifiers: Organ transplant, Stroke, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

385 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called JNJ-90014496, a type of CAR-T cell therapy, for individuals with certain types of non-Hodgkin's lymphoma. The main goal is to determine if this treatment can help when other treatments have failed or if the disease returns. It specifically targets individuals whose lymphoma hasn't responded to at least two other treatments or who have high-risk diffuse large B-cell lymphoma that didn't improve after initial chemotherapy. Participants should have previously confirmed lymphoma with specific markers (CD19 and/or CD20 positive) and have tried other treatments without lasting success. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that the CAR-T therapy called C-CAR039, also known as JNJ-90014496, appears safe. This treatment targets specific proteins, CD19 and CD20, found on some cancer cells. Earlier studies showed that patients with non-Hodgkin's lymphoma, who did not respond to other treatments, tolerated this therapy well.

While some side effects occurred, they were generally manageable, allowing doctors to address any issues during treatment. These studies are in the early stages, focusing on safety and determining the right dose.

In summary, the safety data suggests that C-CAR039 is generally well-tolerated. However, like any treatment, side effects can occur, so discussing these with a doctor is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Non-Hodgkin's Lymphoma, like chemotherapy and monoclonal antibodies, C-CAR039 is a CAR-T cell therapy that uses genetically engineered T-cells to target and destroy cancer cells. Researchers are excited because this treatment reprograms the patient's own immune cells to recognize and attack lymphoma cells specifically, potentially leading to more effective and longer-lasting responses. Additionally, CAR-T therapies have shown promise in cases where other treatments have failed, offering hope for a more personalized and potent approach to fighting this cancer.

What evidence suggests that this treatment might be an effective treatment for non-Hodgkin's lymphoma?

Research has shown that C-CAR039, a new type of CAR-T cell therapy, holds promise for treating B-cell non-Hodgkin lymphoma. This treatment targets two proteins, CD19 and CD20, found on cancer cells. In studies, patients with recurrent or hard-to-treat lymphoma experienced positive outcomes. Specifically, 47.8% of patients continued to respond well to the treatment over time. Participants in this trial will receive an intravenous infusion of C-CAR039, also known as JNJ-90014496, on Day 1. These findings suggest that C-CAR039 could be a viable option for individuals facing these challenging types of lymphoma. ^{1 2 3 6 7}

Who Is on the Research Team?

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Are You a Good Fit for This Trial?

Adults with B-Cell non-Hodgkin lymphoma that has come back or didn't respond after at least two standard treatments can join. They must be over 18, have a certain level of physical fitness (ECOG status 0 or 1), and their major organs need to function well. People with recent serious blood clots, active severe infections, other cancers within the last five years (except some skin or in situ cancers), pregnant women, and those with certain heart conditions cannot participate.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

My tumor is confirmed to be CD19 or CD20 positive.

I have been diagnosed with a type of aggressive large B cell lymphoma or follicular lymphoma.

Exclusion Criteria

I had a blood clot in my leg or lung in the last 6 months.

I had a stem cell transplant less than 12 weeks before my CAR T cell treatment.

I have been diagnosed with a specific type of lymphoma linked to the HHV-8 virus.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an intravenous infusion of autologous JNJ-90014496 on Day 1

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety, effectiveness, and pharmacokinetics after treatment

24 months

Long-term follow-up

Participants are monitored for overall survival and progression-free survival

3 years

What Are the Treatments Tested in This Trial?

Interventions

• C-CAR039

Trial Overview The trial is testing JNJ-90014496, an experimental CAR T-cell therapy targeting CD19 and CD20 proteins on cancer cells. It's for adults whose aggressive B-cell non-Hodgkin lymphoma hasn't been cured by previous treatments. This Phase Ib study is open-label, meaning everyone knows they're getting the test treatment.

How Is the Trial Designed?

Group I: JNJ-90014496 Experimental Treatment 1 Intervention

Participants will receive intravenous (IV) infusion of autologous JNJ-90014496 on Day 1.

C-CAR039 is already approved in United States, China for the following indications:

Approved in United States as C-CAR039 for:

• Relapsed or refractory B-cell non-Hodgkin lymphoma (r/r B-NHL)
• Follicular lymphoma

Approved in China as C-CAR039 for:

• Relapsed or refractory B-cell non-Hodgkin lymphoma (r/r B-NHL)

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Cellular Biomedicine Group Ltd.

Lead Sponsor

Trials

32

Recruited

1,600+

Cellular Biomedicine Group, Inc.

Lead Sponsor

Trials

3

Recruited

270+

City of Hope Medical Center

Collaborator

Trials

614

Recruited

1,924,000+

Published Research Related to This Trial

Chimeric antigen receptor (CAR) T-cell therapy, specifically anti-CD19 CAR T-cell therapies like axicabtagene ciloleucel and tisagenlecleucel, have been approved for treating relapsed or refractory aggressive B-cell lymphoma, marking a significant advancement after decades of limited treatment options.

These therapies have shown promising efficacy in clinical trials, but they also come with potential toxicities, highlighting the need for ongoing research to enhance their safety and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The promise of CAR T-cell therapy in aggressive B-cell lymphoma. Nair, R., Neelapu, SS.[2021]

In the phase II JULIET trial, the CAR T-cell therapy tisagenlecleucel targeting CD19 demonstrated durable responses in patients with relapsed and refractory diffuse large B-cell lymphoma, with 32% achieving complete responses at 3 months.

The efficacy remained stable at 6 months, with 30% of patients still showing complete responses, indicating the potential long-term effectiveness of this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Value in Using CAR T Cells for DLBCL. [2019]

The three CAR-T cell therapies (axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel) show promising efficacy in treating large B cell lymphoma, with overall response rates of nearly 70% and complete response rates exceeding 50% across 33 studies involving 2,172 patients.

However, axicabtagene ciloleucel and tisagenlecleucel are associated with significant risks of severe neurotoxicity and life-threatening cytokine release syndrome, necessitating careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of CAR-T Cell Products Axicabtagene Ciloleucel, Tisagenlecleucel, and Lisocabtagene Maraleucel for the Treatment of Hematologic Malignancies: A Systematic Review and Meta-Analysis. Meng, J., Wu, X., Sun, Z., et al.[2022]

In a phase II study involving 45 chemotherapy-naive patients with carcinoma of unknown primary site (CUP), the combination of irinotecan and carboplatin showed an objective response rate of 41.9%, indicating significant efficacy in treating this rare cancer.

The treatment resulted in a median survival of 12.2 months, with manageable but notable side effects, including neutropaenia and leukopaenia, suggesting that this regimen could be a viable option for patients with CUP who have a good performance status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan plus carboplatin for patients with carcinoma of unknown primary site. Yonemori, K., Ando, M., Yunokawa, M., et al.[2023]

Axicabtagene ciloleucel and tisagenlecleucel are effective CAR T-cell therapies targeting CD19 for treating B-cell acute lymphoblastic leukemia and non-Hodgkin lymphoma, but they can lead to serious complications like cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).

ICANS can occur alongside CRS and may affect the central nervous system due to elevated cytokine levels, but there is currently no consensus on the best management strategies for this condition, highlighting the need for improved identification and treatment protocols in intensive care settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-Cell-Associated Neurotoxicity: Current Management and Emerging Treatment Strategies. Rivera, AM., May, S., Lei, M., et al.[2021]

In a study of 28 patients with platinum-resistant recurrent ovarian cancer, combination therapy with irinotecan and platinum showed a 14% overall response rate, with a clinical benefit rate of 68% when including stable disease.

While the treatment was associated with significant adverse events, particularly hematological issues in 68% of patients, these were manageable, suggesting that CPT-Pt could be a viable option for patients in this challenging clinical setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of irinotecan and platinum for platinum-resistant or refractory recurrent ovarian cancers: A preliminary case series. Shibutani, T., Takano, M., Miyamoto, M., et al.[2020]

In a pivotal phase 2 study involving 93 adult patients with relapsed or refractory diffuse large B-cell lymphoma, CAR T-cell therapy with tisagenlecleucel achieved a best overall response rate of 52%, with 40% of patients experiencing complete responses.

The treatment demonstrated durable responses, with a 12-month relapse-free survival rate of 65%, and no deaths were attributed to the therapy itself, although some patients experienced significant adverse events like cytokine release syndrome and infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma. Schuster, SJ., Bishop, MR., Tam, CS., et al.[2019]

In a phase 2 trial involving 153 patients with relapsed or refractory indolent non-Hodgkin lymphoma, axicabtagene ciloleucel CAR T-cell therapy demonstrated a high overall response rate of 92%, with 74% achieving a complete response, indicating its efficacy in this patient population.

The treatment had a manageable safety profile, with the most common severe adverse events being cytopenias and infections, and only 3% of patients experiencing treatment-related deaths, suggesting that while there are risks, the benefits may outweigh them for many patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axicabtagene ciloleucel in relapsed or refractory indolent non-Hodgkin lymphoma (ZUMA-5): a single-arm, multicentre, phase 2 trial. Jacobson, CA., Chavez, JC., Sehgal, AR., et al.[2022]

In the RELIANCE study involving 68 patients with heavily pre-treated relapsed/refractory large B-cell lymphoma, relmacabtagene autoleucel (relma-cel) showed a high objective response rate of 77.59% and a complete response rate of 53.45% after a median follow-up of 17.9 months.

The treatment demonstrated a manageable safety profile, with only 5.1% of patients experiencing severe cytokine release syndrome and 3.4% experiencing severe neurotoxicity, indicating that relma-cel is both effective and relatively safe for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcomes of relmacabtagene autoleucel in Chinese patients with relapsed/refractory large B-cell lymphoma: Updated results of the RELIANCE study. Ying, Z., Yang, H., Guo, Y., et al.[2023]

Tisagenlecleucel and axicabtagene ciloleucel are groundbreaking CAR-T cell therapies that have shown high effectiveness in treating relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) and certain types of B-cell non-Hodgkin lymphomas.

This review highlights the challenges faced by physicians in administering these therapies and discusses future directions for research and treatment in the field of immune and cellular therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19 chimeric antigen receptor-T cells in B-cell leukemia and lymphoma: current status and perspectives. Mohty, M., Gautier, J., Malard, F., et al.[2022]

Anti-CD19 CAR T-cell therapy has shown remarkable efficacy in treating relapsed or refractory aggressive B-cell lymphomas, leading to durable remissions in patients who previously had no effective treatment options.

Three CAR T-cell therapies (axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel) are approved for use, each differing in their design, manufacturing processes, and safety profiles, highlighting the need for personalized approaches in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD19 CAR T-Cell Therapy for B-Cell Non-Hodgkin Lymphoma. Abramson, JS.[2021]

CAR T-cell therapy, particularly with anti-CD19 targeting, has shown significant effectiveness in treating aggressive B-cell non-Hodgkin's lymphoma (NHL), leading to long-term remissions in patients with diffuse large B-cell lymphoma (DLBCL) who have not responded to other treatments.

Two CAR T-cell products, axicabtagene ciloleucel and tisagenlecleucel, have been approved by the FDA for refractory DLBCL, while a third product, liso-cel, is showing promising results in ongoing trials, although potential side effects like cytokine-release syndrome and neurotoxicity are important considerations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-cell therapy for B-cell lymphomas: clinical trial results of available products. Chavez, JC., Bachmeier, C., Kharfan-Dabaja, MA.[2020]

In a phase II study involving 29 patients with refractory or relapsed small cell lung cancer, the combination of irinotecan (CPT-11) and carboplatin showed a 31% overall response rate, indicating it can be an effective second-line treatment option.

While the treatment demonstrated activity, it also had significant toxicity, with 52% of patients experiencing severe neutropenia and one treatment-related death, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of weekly irinotecan and carboplatin for refractory or relapsed small-cell lung cancer. Naka, N., Kawahara, M., Okishio, K., et al.[2019]

In a study involving 9 patients with cervical cancer, combination therapy using irinotecan and nedaplatin showed a 40% response rate in patients receiving treatment before surgery and a 75% response rate in those with recurrent disease.

While the treatment was effective, it also led to significant side effects, including grade 3 or 4 adverse events such as leukopenia in 4 patients, indicating the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Combined irinotecan (CPT-11) and nedaplatin (254-S) therapy for advanced and/or recurrent cervical cancer]. Hiruma, R., Kamide, T., Anzai, N., et al.[2018]

Citations

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A phase 1 trial of prizloncabtagene autoleucel, a CD19/CD20 ... Furthermore, B-cell recovery was observed in 47.8% patients with ongoing responses, suggesting that durable responses in patients with lymphoma ...

2. jnj.com jnj.com/media-center/press-releases/johnson-johnsons-dual-targeting-car-t-cell-therapy-shows-encouraging-first-results-in-large-b-cell-lymphoma

Johnson & Johnson's dual-targeting CAR T-cell therapy ... A Phase 1 study for C-CAR039 was conducted in China for the treatment of patients with B-cell non-Hodgkin lymphoma (predominantly LBCL).

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39813680/

A phase 1 trial of prizloncabtagene autoleucel, a CD19/ ... This phase 1, open-label study investigated the safety and efficacy of prizlon-cel in patients with relapsed/refractory B-cell non-Hodgkin Lymphoma (r/r B-NHL).

4. abelzeta.com abelzeta.com/wp-content/uploads/2024/01/AbelZeta-CAR039-ASH-2023-presentation.pdf

C-CAR039, a Novel Anti-CD20/CD19 Bi-Specific – The median time to B cell recovery was 185.0 days. Page 12. Conclusions. • C-CAR039 is a novel bispecific CAR-T targeting CD19 and CD20 B-Cell antigens. • C ...

5. library.ehaweb.org library.ehaweb.org/eha/2024/eha2024-congress/document?c_id=419562&cm_id=434395&type=document434395

c-car039, a novel anti-cd20/cd19 bi-specific car t-cell ... C-CAR039, an autologous anti-CD20/CD19 bispecific CAR-T, previously demonstrated a favorable safety profile and promising efficacy among 28 patients. (pts) with ...

6. ashpublications.org ashpublications.org/blood/article/145/14/1444/536405/Prizloncabtagene-autoleucel-a-new-CAR-T-cell-for-B

Prizloncabtagene autoleucel: a new CAR T cell for B-NHL The results of the phase 1 trial of prizlon-cel, a bispecific CAR T-cell therapy targeting both CD19 and CD20, conducted by Yu and colleagues, ...

7. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/397356

A Study of C-CAR039 (Prizloncabtagene Autoleucel) in ... This is a multicenter, single arm, open-label study. The purpose of the study is to evaluate safety of Prizloncabtagene Autoleucel (Prizlon-cel) and ...